rs288980

Positions:

• chr18-21029619-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005406.3(ROCK1):​c.1052-684A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 151,966 control chromosomes in the GnomAD database, including 34,816 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (34816 hom., cov: 31)
• Consequence: ROCK1 NM_005406.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.742

Genes affected

ROCK1 (HGNC:10251): (Rho associated coiled-coil containing protein kinase 1) This gene encodes a protein serine/threonine kinase that is activated when bound to the GTP-bound form of Rho. The small GTPase Rho regulates formation of focal adhesions and stress fibers of fibroblasts, as well as adhesion and aggregation of platelets and lymphocytes by shuttling between the inactive GDP-bound form and the active GTP-bound form. Rho is also essential in cytokinesis and plays a role in transcriptional activation by serum response factor. This protein, a downstream effector of Rho, phosphorylates and activates LIM kinase, which in turn, phosphorylates cofilin, inhibiting its actin-depolymerizing activity. A pseudogene, related to this gene, is also located on chromosome 18. [provided by RefSeq, Aug 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROCK1	NM_005406.3	c.1052-684A>G		intron_variant		ENST00000399799.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROCK1	ENST00000399799.3	c.1052-684A>G		intron_variant		1	NM_005406.3	P1
ROCK1	ENST00000635540.2	c.1052-684A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99460 AN: 151850 Hom.: 34743 Cov.: 31

Gnomad AFR AF: 0.911

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.633

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.655 AC: 99593 AN: 151966 Hom.: 34816 Cov.: 31 AF XY: 0.657 AC XY: 48819 AN XY: 74284

Gnomad4 AFR AF: 0.911

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.581

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.638

Alfa AF: 0.561 Hom.: 31749

Bravo AF: 0.673

Asia WGS AF: 0.644 AC: 2234 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs288980; hg19: chr18-18609580;